Clinical Trial Details
— Status: Not yet recruiting
Administrative data
| NCT number |
NCT06429475 |
| Other study ID # |
BREC/00005663/2023 |
| Secondary ID |
|
| Status |
Not yet recruiting |
| Phase |
Phase 3
|
| First received |
|
| Last updated |
|
| Start date |
May 25, 2024 |
| Est. completion date |
May 28, 2026 |
Study information
| Verified date |
March 2024 |
| Source |
University of KwaZulu |
| Contact |
Refiloe Masekela, PhD |
| Phone |
+27794890936 |
| Email |
masekelar[@]ukzn.ac.za |
| Is FDA regulated |
No |
| Health authority |
|
| Study type |
Interventional
|
Clinical Trial Summary
This is a Phase 3 single-centre open label randomised controlled trial with two equal sized
groups to assess the efficacy of budesonide/formoterol 80/4.5 (6-11 years) and 160/4.5 (12-18
years) compared to the standard of care in reducing asthma exacerbations over 52 weeks.
Children and adolescents with a diagnosis of asthma or newly diagnosed with asthma will be
screened for eligibility for enrolment. Those who had an asthma exacerbation in the previous
year will be randomised 1:1, to either receive budesonide/formoterol inhaler for both symptom
relief and for chronic anti- inflammatory maintenance therapy or the standard of care which
is separate inhalers for symptom relief (short acting bronchodilator salbutamol) and chronic
maintenance therapy with inhaled corticosteroids (beclomethasone or budesonide) and/or
long-acting beta agonists or montelukast as determined by treating physicians. All asthma
exacerbations and clinic/hospital admissions will be recorded for the duration of the 52-week
follow-up. Participants will be followed up at 13, 26, 39 and 52 weeks. The 13- and 39-week
visit will be telephonic visits to capture the primary end-point i.e. asthma exacerbations.
Adverse events and medication changes data will also be collected.
An independent Data and Safety Monitoring Board (DSMB) will be convened for this study with
expertise in asthma and asthma clinical trials. The purpose of the DSMB will be to monitor
the study for safety and operational futility with pre-defined stopping criteria. In
addition, a Trial Steering Committee (TSC) will also provide overall supervision of the trial
and ensure the trial is delivered in accordance with ICH-GCP. The TSC has been established
with an independent Chair and include additional independent members including an observer
early career researcher. Representatives of the Trial Funder (NIHR) and Sponsor (AHRI) will
be invited to all TSC meetings.
Description:
Over the last two decades non-communicable diseases (NCDs) have been rising in sub-Saharan
Africa, and NCDs are set to overtake communicable, maternal, neonatal, and nutritional
diseases combined as the leading cause of mortality in sub-Saharan Africa by 2030. Many NCDs
have their roots in childhood with lifestyle changes in combination with an increasing median
population age in Africa making a further dramatic rise in NCDs in Africa's near future
highly likely. The World Health Organization (WHO) now considers the prevention and control
of NCDs as an urgent development issue and essential to the achievement of the Sustainable
Development Goals (SDG) and this can only be achieved with childhood interventions. The 2018
WHO report on NCDs, reported 3.8 million deaths annually from non-communicable respiratory
diseases (asthma and chronic obstructive pulmonary disease), with 78% of deaths in low-income
and middle-income countries (LMICs). Asthma morbidity and mortality are preventable with
inhaled therapies-however, there is lack of evidence on how to deliver these in an affordable
and effective way.
The WHO highlights asthma as an under-appreciated cause of poverty in LMICs that retards
economic and social development, erodes the health and well-being of those affected and has a
negative impact on families and societies. Asthma aggravates poverty and poverty aggravates
asthma. Children miss out on education, adults lose days at work and the costs of drugs,
emergency visits, and hospitalization are major financial burdens, not only for
individuals/families but also for struggling health systems.
In South Africa, asthma is the most common NCD in childhood affecting 1 in 5 children with a
prevalence of asthma symptoms at 21% in adolescence. Despite the availability of asthma
medicines in the Essential Medicines List, asthmatic children report having severe asthma
symptoms in over 50% of those with asthma. South Africa still reports the fourth highest
mortality rate globally. The core to asthma management includes use of chronic use of
anti-inflammatory inhaled corticosteroids to address the inflammatory process in the airways
(maintenance) and bronchodilators (relievers) for relief of the bronchospasm. Many studies
have shown that asthma mortality is linked to poor use of anti-inflammatory inhaler treatment
and over-reliance on short- acting β2 bronchodilator reliever therapy to treat asthma
exacerbations. In many LMICs including South Africa, the use of controller treatment use of
anti-inflammatory inhalers is limited, with only 40% of people with severe asthma symptoms
using regular ICS for chronic asthma treatment, but with over 89% using their short-acting β2
agonists. There is a large body of evidence showing that overuse of SABAs is linked with
asthma mortality and poorer outcomes.
The combination treatment with budesonide/formoterol for the management of asthma has
transformed asthma treatment in high-income countries (HIC), where it is recommended in the
very first step of asthma treatment as both an anti-inflammatory and reliever therapy. With
the "as needed" use of budesonide/formoterol, asthmatics benefit from the additional dose of
a maintenance anti-inflammatory dose, which improves symptom control and reduces
exacerbations. This approach has not been adopted in many LMICs related to access to
budesonide/formoterol and its cost and therefore, people in LMICs are relegated to use of
Track 2 of Global Initiative of Asthma (GINA) treatment which still suggests the use of
separate anti-inflammatory and reliever inhalers.
To address this gap, a large body of randomized controlled clinical trial evidence (SYGMA,
Novel START, PRACTICAL, and several trials of SMART), have shown that use of
budesonide/formoterol as needed (for exacerbations) and for long-term controller treatment
compared to separate inhaled corticosteroid and short-acting bronchodilators, reduces the
number of asthma exacerbations and improves quality of life. The trials have though been
limited in that there is no data on the cost-effectiveness of this approach in lower
resourced settings and limited data from small studies participant numbers (<100) of this
approach in children 6-11 years of age. Based on this, the approach of using
budesonide/formoterol has not been recommended by the Global Initiative of Asthma (GINA)
strategy for global asthma management in Step 1 and 2 of treatment in children 6-11 years of
age both in HIC and LMICs, but rather on the higher steps of asthma treatment where symptoms
are more severe.
The investigators therefore propose in a randomized controlled trial to assess the efficacy
of budesonide/formoterol compared to the standard of care (separate inhaled corticosteroid
and bronchodilator) inhaler approach to prevent asthma exacerbations, improve asthma control
and quality of life and to also assess the cost-effectiveness of budesonide/formoterol
compared to standard of care in children and adolescents in South Africa. The data will be
novel as the investigators will for the first time include a large number of children in a
clinical trial comparing the two approaches, to provide definitive evidence of the efficacy
and cost-effectiveness of this approach in children and adolescents.
